Page 4 - M. Immunology

[M. Immunology-3]

Identification of the in vivo role of Tetraspanin 7 in

osteoclastic bone resorption

Minhee Kim¹, Jingjing Lin¹, Doori Park¹, Sooyoung Lee¹˙*

¹Life Science, Ewha Womans University, Seoul 03760, Republic of Korea

Bone growth and maintenance are tightly regulated by bone forming osteoblasts and bone resorbing osteoclasts.
Upon macrophage colony-stimulating factor (M-CSF) and receptor for activation of nuclear factor kappa B (NF-κB)
(RANK) ligand (RANKL) signaling, osteoclast precursors differentiate into osteoclasts. Once osteoclasts form actin

rich, adhesive structures, they degrade bone matrix. In our previous study, we revealed that Tetraspanin 7 (Tspan7)

links RANK/αvβ3 integrin complex and acts as a key regulatory factor for osteoclast function. Recently, we generated
Tspan7 knockout (Tspan7-/-) mice using CRISPR/Cas9 system and here elucidated its role in bone development.
Bone-resorbing activity of osteoclasts was reduced in Tspan7-/- mice owing to a defect in actin ring formation, but

there was no difference in osteoclast formation. Mice with Tspan7 deletion showed significantly increased cortical
bone quality. Surprisingly, Tspan7-/- mice exhibited decreased bone erosion in vivo in both lipopolysaccharide (LPS)-

and ovariectomy (OVX)- induced osteoporosis models. Taken together, our results suggest that Tspan7-/- mice have
defective osteoclast function and therefore may be a novel therapeutic model to treat the pathological bone loss.